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| Targets |
CDK8-IN-1 targets cyclin-dependent kinase 8 (CDK8), a component of the Mediator complex that regulates RNA polymerase II transcriptional activity. CDK8 is involved in transcriptional regulation, cell cycle control, and various signaling pathways. Inhibition of CDK8 with an IC50 of 3 nM modulates transcription of target genes. The compound shows selectivity for CDK8 over other kinases.
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| ln Vitro |
CDK8-IN-1 demonstrates potent in vitro inhibition of CDK8 with an IC50 of 3 nM. The compound shows selective inhibition of CDK8 enzymatic activity. As a small molecule kinase inhibitor, it effectively blocks CDK8-mediated phosphorylation of substrates. The compound exhibits good potency in biochemical assays. Purity is typically >97%.
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| ln Vivo |
Oral bioavailability, excellent exposure, and low systemic clearance were demonstrated by CDK8-IN-1. Tmax for PO is 0.25 hours. IV and PO had respective average Cmax values of 9940 μg/L and 12740 μg/L. According to IV and PO, the computed AUC values are 9378 and 25952, respectively [1].
In vivo, CDK8-IN-1 demonstrates favorable pharmacokinetic properties including low systemic clearance, very good exposure, and oral bioavailability. Following oral administration, the tmax is 0.25 hours. The AUC values are 9378 for intravenous administration and 25952 for oral administration. The mean Cmax values are 9940 for intravenous administration. These properties support its use in in vivo studies. |
| Enzyme Assay |
In vitro enzyme assays for CDK8-IN-1 typically employ recombinant CDK8/Cyclin C kinase and appropriate peptide substrates. Kinase activity is measured using radioactive ATP (33P-ATP) or fluorescence-based detection methods such as ADP-Glo™ assay. Reactions are performed in kinase buffer at optimized ATP concentrations. The IC50 value of 3 nM is determined by measuring remaining kinase activity across a range of inhibitor concentrations. Assays are performed in triplicate with appropriate controls.
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| Cell Assay |
Cellular assays for CDK8-IN-1 involve treating cancer cell lines with varying concentrations of the compound (typically 0.001-10 microM range) for 24-72 hours. Readouts include cell viability measured by MTT or CellTiter-Glo assays, assessment of CDK8 downstream target gene expression by qPCR or Western blotting, and evaluation of transcriptional activity using reporter assays. Phosphorylation of CDK8 substrates is assessed by Western blotting.
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| Animal Protocol |
Dose-response studies in animal models for CDK8-IN-1 typically involve oral administration in rodent models. Pharmacodynamic studies assess target engagement and modulation of downstream biomarkers. Efficacy studies in disease models (e.g., cancer xenografts) involve daily oral dosing at various doses. Tumor growth inhibition, biomarker modulation, and survival are monitored. The compound's oral bioavailability supports convenient dosing regimens.
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| ADME/Pharmacokinetics |
CDK8-IN-1 exhibits favorable pharmacokinetic properties. It displays low systemic clearance and very good compound exposure. Following oral administration, the tmax is 0.25 hours. AUC values are 9378 (IV) and 25952 (PO), with mean Cmax values of 9940 (IV). These PK parameters indicate good oral bioavailability and excellent exposure profiles. The compound's molecular weight of 255.20 suggests favorable drug-like properties.
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| Toxicity/Toxicokinetics |
Toxicological data for CDK8-IN-1 is limited to research-grade handling information. As a kinase inhibitor, potential toxicities may include off-target effects. The compound shows favorable PK properties suggesting a reasonable safety profile. Standard safety precautions should be observed during handling including appropriate PPE and work in a fume hood. Comprehensive toxicology studies would be required for clinical development. The compound is for research use only.
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| References | |
| Additional Infomation |
CDK8-IN-1 (CAS# 1629633-48-2) is a potent and selective CDK8 inhibitor used as a research tool. It has been studied for its potential in cancer therapy, as CDK8 is implicated in various malignancies. The compound demonstrates excellent oral bioavailability and favorable PK properties. It is typically stored at -20degC. CDK8-IN-1 is not approved for clinical use and is intended for research purposes only. The compound is available in research-grade purity (>97-98%).
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| Molecular Formula |
C11H8F3N3O
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|---|---|
| Molecular Weight |
255.195932388306
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| Exact Mass |
255.061
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| CAS # |
1629633-48-2
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| PubChem CID |
86274989
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| Appearance |
White to light brown solid powder
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| LogP |
1.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
18
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| Complexity |
315
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC(C1=C(C(N)=O)NC=C1C1C=CN=CC=1)(F)F
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| InChi Key |
RKTPHHQXNCHBCF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H8F3N3O/c12-11(13,14)8-7(5-17-9(8)10(15)18)6-1-3-16-4-2-6/h1-5,17H,(H2,15,18)
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| Chemical Name |
4-pyridin-4-yl-3-(trifluoromethyl)-1H-pyrrole-2-carboxamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~391.85 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.9185 mL | 19.5925 mL | 39.1850 mL | |
| 5 mM | 0.7837 mL | 3.9185 mL | 7.8370 mL | |
| 10 mM | 0.3918 mL | 1.9592 mL | 3.9185 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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